Variant CYP2C9 alleles and warfarin concentrations in patients receiving low-dose versus average-dose warfarin therapy.

This study compared the frequency of variant cytochrome P450 2C9 (CYP2C9) alleles and warfarin S/R concentration ratio in patients who required low-dose (<2.5 mg/day) and average-dose (5+/-0.5 mg/day) warfarin. Patients who achieved a therapeutic international normalized ratio were recruited from the Atlanta Veterans Affairs Medical Center anticoagulation clinic. CYP2C9*2 and *3 alleles were determined by validated Taqman allelic discrimination assays. Warfarin S and R concentrations were determined by chiral capillary electrochromatography with electrospray ionization mass spectrometry. At least 1 variant allele was found in 66.7% and 22.2% of patients in the low-dose and average-dose groups, respectively (P= .001, chi(2)). The warfarin S/R concentration ratio was 0.665 (range, 0.162-3.58) and 0.452 (range, 0.159-2.36) for patients receiving low-dose and average-dose therapy, respectively (P= .097). A warfarin requirement of <2.5 mg/day and an elevated warfarin S/R concentration ratio were each associated with a higher frequency of variant CYP2C9 alleles.

CYP2C9 genetic polymorphisms and warfarin.

The objective of this study was to report 2 cases of CYP2C9 genetic polymorphism and elevated warfarin S:R ratios in patients taking low doses of warfarin, and compare the observed characteristics with those in published reports. Two patients of different age groups and races were evaluated for CYP2C9 genotype and warfarin S:R ratios. The patients had been stabilized on weekly warfarin doses of 10.5 mg and 10 mg, respectively. Each patient was found to have at least 1 variant CYP2C9 allele. Elevated warfarin S:R ratios in both patients provided evidence for impaired metabolism of S-warfarin. This report of a CYP2C9*3 heterozygous individual taking a low dose of warfarin is consistent with previous reports in the literature. This summary of a CYP2C9*6 homozygous individual taking a low dose of warfarin is the first such published report. CYP2C9 genotyping in these patients provided a likely explanation for their continued low warfarin dosage requirements. Awareness of a patient's CYP2C9 genotype may provide an explanation for low warfarin dosage requirements in stable patients and may help in determining the optimal dose in patients being initiated on warfarin.

Aggrenox((R)) versus other pharmacotherapy in preventing recurrent stroke.

Stroke is the third leading cause of death in the US with recurrent events a high likelihood in those who survive an initial event. The long-term goal of therapy is to prevent the recurrence of stroke and other atherosclerotic events. Aspirin has been the first-line agent for stroke prevention for a long time. As new antiplatelet agents have been introduced, their role in the secondary prevention of stroke remains to be defined. In particular, the role of the combination of aspirin and modified-release dipyridamole (Aggrenox, Boehringer Ingelheim Corp.), the newest product, in the secondary prevention of stroke, remains unknown. The purpose of this manuscript is to review the evidence of these antiplatelet agents in the secondary prevention of stroke and arrive at a conclusion specifically regarding the role of Aggrenox. Clinical studies which examined stroke as a single primary outcome or as one event in a combined primary outcome will be reviewed.

Chromium as adjunctive treatment for type 2 diabetes.

OBJECTIVE: To review the chemistry, pharmacology, efficacy, and safety of trivalent chromium in the treatment of type 2 diabetes and hyperlipidemia. DATA SOURCES: The English literature was searched from 1966 through May 2002 using MEDLINE, International Pharmaceutical Abstracts, and EMBASE. The key words included chromium, glucose, lipids, and diabetes. Pertinent references from review articles and studies were used as additional sources. DATA SYNTHESIS: Trivalent chromium is an essential nutrient and has a key role in lipid and glucose metabolism. Supplementation with chromium does not appear to reduce glucose levels in euglycemia. It may, however, have some efficacy in reducing glucose levels in hyperglycemia. The effects of chromium on lipid levels are variable. Chromium in doses <1000 microg/d appears to be safe for short-term administration. Kidney function and dermatologic changes need to be monitored. CONCLUSIONS: Chromium appears to be a safe supplement and may have a role as adjunctive therapy for treatment of type 2 diabetes. Additional large-scale, long-term, randomized, double-blind studies examining the effect of various doses and forms of chromium are needed.

Warfarin versus aspirin in the secondary prevention of stroke: the WARSS study.

The role of anticoagulation in the secondary prevention of noncardioembolic stroke has long been an area of debate. Previous evidence has shown that anticoagulation is unsafe at an International Normalized Ratio between 3.0 and 4.5. Results of the recently published Warfarin-Aspirin Recurrent Stroke Study (WARSS) suggest that there is no difference between warfarin and aspirin in the prevention of recurrent ischemic stroke or death or in the rate of major hemorrhage. Differences in the therapeutic interventions used may have had an effect on the differences in endpoints achieved as compared with previous studies. Results of ongoing trials are anticipated to further clarify the role of anticoagulation in the secondary prevention of stroke.